The present invention relates to a device for setting the temperature of at least one sample to different values, the device comprising a holder intended to receive the sample, temperature-adjusting means which are thermostatted to at least two different temperatures, transport means for the holder and a control system for the transport means, the arrangement being such that the sample can be brought into thermal contact selectively with any of the temperature-adjusting means.
A device of the afore mentioned kind is known from U.S. Pat. No. 4,632,808.
It is a requirement of many biochemical methods that the temperature of solutions must be changed quickly and in a reproducible way, for example for the purpose of heat-denaturating nucleic acids, annealing primers, starting or stopping enzymatic reactions, and the like. Frequently, it is also necessary for such reactions that a pre-determined temperature profile cycle be run through, which may comprise several heating-up or cooling-down phases. The duration of such an experiment may be up to several hours. Similar tasks are encountered also in other fields of science and technology.
It is desirable to automate such processes in order to take some of the load off the personnel and to guarantee reproducible conditions.
There have been known devices comprising a metal block which contains bores or recesses intended to receive reaction vessels made from a plastic material and whose temperature can be adjusted to the desired values. The reaction vessels are thermostatted by their contact with the walls of such bores; the contact may be improved by filling the bores with water or oil. The temperature of the metal block can be adjusted, for example, with the aid of heating cartridges which are controlled in response to a constantly operating water or convection cooling system. Another possibility consists in the use of Peltier elements for heating and cooling the metal block. Another known method for thermostatting the metal block consists in the use of thermostatting baths of different temperatures which can be selectively connected, via a valve system, with fluid channels provided in the metal block.
However, due to the considerable heat storage capacity of the metal block and of the system connected to the latter, it is rather difficult to achieve rapid temperature changes in the case of such set-ups.
The before-mentioned U.S. Pat. No. 4,632,808 describes a chemical manipulator which is capable of carrying out automatically a number of mixing, separating, heating and cooling steps. The device comprises for this purpose a centrifugal separator, four thermostat baths which are open at their tops, a drying system, a solution adding station, a mixing station and transport means. The transport means comprises a robot arm which is capable of being displaced in the three directions in space and which is controlled by a control system.
The samples to be examined are contained in plastic reaction vessels which can be accommodated in a box-like holder by groups of four. The known device uses a plurality of such holders which are transported by the robot arm to the different processing stations, as directed by the control. For heating or cooling the samples, the holders are dipped into the desired thermostat bath which latter contains suitable means for receiving the holders.
With the aid of this arrangement, the temperature change can be brought about in the samples only slowly due to the fact that the movement which the robot arm has to perform in order to pick up the holder from one thermostat bath and suspend it in another thermostat bath is along several axes and, thus, slow. Consequently, the time between the removal of the holder from one bath, and its introduction into the next thermostat bath is far too long as to permit, for example, to stop enzymatic reactions within the required short time of a few seconds.
In addition, it is a disadvantage of the known device that the samples get into thermal contact with the ambient air on their way between two thermostat baths. If the samples are to be heated up, for example, from 70.degree. Centigrade to 90.degree. Centigrade, as is the case with many enzymatic reactions where such temperature changes have to be brought about cyclically, the samples which have been heated up to 70.degree. Centigrade will be cooled down excessively on their way through the air. This has a negative influence on the yield of the reaction.
The open thermostat baths lead in addition to problems due to splashing or dripping of the bath liquid.
From U.S. Pat. No. 3,801,467 there has been known a vibrator for cultivating microorganisms where an aluminium block is set into vibrating movement. The aluminium block is heated on its one end and cooled on its other end so that a temperature gradient develops along the block. The block is further provided with grooves extending in parallel to its longitudinal direction, i.e. in the direction of the temperature gradient, and further with a plurality of bores. It is said that in the case of the known device only short time is required for building up the temperature gradient so that a broad and continuous temperature range is made available for cultivating the microorganisms.
The grooves and bores serve for accommodating steel Petri dishes or glass flasks containing the microorganisms to be cultivated. The Petri dishes or glass flasks can be inserted into the grooves or bores in those positions which have the correct temperature required for the respective cultivation task. It is thus possible to incubate several cultures at different temperatures all at the same time.
Changing the temperature of the cultures during the incubation is not envisaged, and would in fact take far too much time, for example for enzymatic reactions, due to the fact that the cultivating vessels consist of steel or glass.
U.S. Pat. No. 3,684,452 describes a device for carrying out analytical processes, in particular for incinerating reagents. In the case of this known device, test tubes containing solutions are held and indexed through their path by an indexing table, an endless conveyor or conveyor chain. One of the stations is equipped with a stationary heating channel through which the test tubes are carried by the transport means. On their way through the channel, the test tubes project downwardly into the U-shaped heating channel which is open at its ends and whose side walls and bottom are equipped with heating coils.
The tubes and, thus, the solutions are heated up by the radiation from the heating coils, the latter being arranged in such a way that the heat increases as the tubes are transported further along and into the channel. The heating channel is followed by a washing and rinsing station where the test tubes are cleaned after incineration of the solutions so that they are immediately available for further use.
This known device does not, however, permit cyclical heating up and cooling down.
U.S. Pat. No. 4,675,509 describes a bonding press for bonding together flat pieces of textile materials, in particular linings or skin materials. The known device comprises a heating station having a plurality of heating zones provided with electric heatings which can be switched on and off selectively so as to enable a desired temperature distribution to be adjusted as a function of space and/or time. The heatings consist of flexible heating mats with embedded heating wires. The pieces of textile material are moved along the heating mats, are heated up by their contact with the latter and are bonded together subsequently.
This known bonding press is not suited for carrying out biochemical processes.